Detection of clonotypic IGH and TCR rearrangements in the neonatal blood spots of infants and children with B-cell precursor acute lymphoblastic leukemia.

Abstract:

:An attractive hypothesis is that in utero exposure of hematopoietic cells to oncogenic agents can induce molecular changes leading to overt acute lymphoblastic leukemia (ALL) in infants and perhaps older children as well. Although supported by studies of identical infant twins with concordant leukemia, and of nontwined patients with MLL gene rearrangements, this concept has not been extended to the larger population of B-lineage ALL patients who lack unique nonconstitutive mutations or abnormally rearranged genes. We therefore sought to demonstrate a prenatal origin for 7 cases of B-cell precursor ALL (either CD10(+) or CD10(-)) that had been diagnosed in infants and children 14 days to 9 years of age. Using a polymerase chain reaction-based assay, we identified the same clonotypic immunoglobulin heavy-chain complementarity determining region or T-cell receptor V(D)2-D(D)3 sequences in the neonatal blood spots (Guthrie card) and leukemic cell DNAs of 2 infants with CD10(-) ALL and 2 of the 5 older patients with CD10(+) ALL. Nucleotide sequencing showed a paucity of N or P regions and shortened D germ line and conserved J sequences, indicative of cells arising from fetal hematopoiesis. Our findings strongly suggest a prenatal origin for some cases of B-cell precursor ALL lacking specific clonotypic abnormalities.

journal_name

Blood

journal_title

Blood

authors

Yagi T,Hibi S,Tabata Y,Kuriyama K,Teramura T,Hashida T,Shimizu Y,Takimoto T,Todo S,Sawada T,Imashuku S

subject

Has Abstract

pub_date

2000-07-01 00:00:00

pages

264-8

issue

1

eissn

0006-4971

issn

1528-0020

journal_volume

96

pub_type

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